NIHNIH……Turning Discovery Into HealthTurning Discovery Into Health

vermam@mail.nih.gov

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NATIONAL INSTITUTES OF HEALTH (NIH)RESEARCH RESOURCES IN

BIOTECHNOLOGY

Mukesh Verma, Ph.D.Chief

Methods and Technologies BranchProgram Director, Epidemiology and Genomics

Research ProgramDivision of Cancer Control and Population Sciences

National Cancer Institute (NCI)National Institutes of Health (NIH)

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Outline

• NIH: Mission and Organization• Different Institutes • National Cancer Institute: an Example• Cancer Prevention and Other Research Priorities at the NCI• Grants: Review Process • Guidelines for Students: Who Would Apply for Funding• RePORT, eRA Commons• Solicited and Unsolicited Grant Applications• Job Opportunities, Fellowships at NIH

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National Institutes of Health www.nih.gov

• NIH is the nation's medical research agency – making important medical discoveries that improve health and save lives.

• The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the primary Federal agency for conducting and supporting medical research.

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www.nih.gov

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National Cancer Institute

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Search Engine

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The NIH invests over $30 billion annually in medical research for the American people.

More than 80% of the NIH’s funding is awarded through almost 50,000 competitive grants to more than 212,000 researchers at over 2,800 universities, medical schools, and other research institutions in every state and around the world.

About 10% of the NIH’s budget supports projects conducted by nearly 6,000 scientists in its own laboratories, most of which are on the NIH campus in Bethesda, Maryland.

NIH Budget

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The NCI Budget Emphasizes Extramural Research

NCI Budget > $4B per year

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• 854 DCCPS grants, totaling over $350M

• 239 competing awards funded in FY 2008 – New R01s = 108– New R21s = 48– New R03s = 53 – All other competing awards = 30

Budget of DCCPS

Breakdown of Budget

Funding research• NIH supports external research in 3 ways:

– Grant: Investigator decides the research design and approach

– Contract: Government decides the research scope to fill need and establishes detailed requirements

– Cooperative Agreement: Similar to grant, BUT both awarding Institute/Center and recipient have substantial involvement in design and conduct of the research

Different Types of Grants

• Small Grants (R03)• Exploratory Grants (R21)• Investigator Initiated Grants (R01)• Program Project Grants (P01)• Cooperative Agreements (U01)• SBIR/STTR (R41/R42/R43/R44)

Grants.govCancer.gov

Multiple PI Mechanism is Applicable in All

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DP1 NIH Director’s Pioneer Award (NDPA)DP2 NIH Director’s New Innovator AwardsDP3 Type 1 Diabetes Targeted Research AwardDP4 NIH Director’s Pathfinder Award- Multi-Yr FundingDP5/UP5 Early Independence Award/Cooperative Agreement

Other Types of Mechanisms

P01/PL1 Program Project Grant/Linked Program ProjectP20 Exploratory GrantsP30 Center Core GrantsP40 Animal (Mammalian and Nonmammalian) Model, and Animal and Biological Material Resource GrantsP41 Biotechnology Resource GrantsP50 Specialized Center

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CSR

http://cms.csr.nih.gov/ResourcesforApplicants/InsidetheNIHGrantReviewProcessVideo.htm

Video of the Review Process:

1-3 Months Submission and assignment

4-6 Months Review and Summary Statement

7-9 Months Human Sub etc and Award

1-3 Months Submission and assignment

4-6 Months Review and Summary Statement

7-9 Months Human Sub etc and Award

Grant Review Process

Major Steps

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Overall Timeframe from Submission to Award

  There are three overlapping cycles per year :

JAN FEB MAR APR MAY JUN JUL AUG SEP OCT NOV DEC JAN FEB MAR APR MAY JUN JUL

Review Council

Cycle 1Receipt

Referral Award

Review Council

Cycle 3ReceiptReferral Award

Review CouncilCycle 2

ReceiptAwardReferral

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Training and FellowshipGrants (T and F Series)

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Cancer Training Grants—K Awards

• Career Development Awards– K07: Cancer Prevention, Control, Behavioral,

and Population Sciences Career Development Award

– K22: NCI Transition Career Development Award

– K23: Mentored Patient-Oriented Research Career Development Award

– K24: Mid-Career Investigator Award in Patient-Oriented Research

– K99/R00: NIH Pathway to Independence Award

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https://commons.era.nih.gov/commons

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Registered Organizations

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Pancreatic Cancer

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DIRECTORY NIH https://ned.nih.gov/search/search.aspx

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Jobs at NIH

http://www.jobs.nih.gov/

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Research Training

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Summer Training

Student

Postdoctoral

http://www.training.nih.gov/

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NCI Strategic PrioritiesSetting Course for Accelerated Progress

• Molecular Epidemiology: Understanding Causes of Cancer

• Early Detection, Prevention, Prediction

• Integrative Cancer Biology

• Strategic Development of Cancer Interventions

• Integrated Clinical Trials System

• Overcoming Health Disparities

• Bioinformatics

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THE CANCER CONTROL CONTINUUM

Prevention

Focus

• Tobacco Control• Diet• Physical Activity• Sun Exposure• Virus Exposure• Alcohol Use• Chemoprevention

Detection• Pap Test• Mammography• FOBT• Endoscopy• PSA Informed

Decision Making

Treatment• Health Services

and Outcomes Research

• Clinical Trials

Survivorship• Palliation• Coping• Health Promotion

Diagnosis• Informed

Decision Making

• Clinical Follow-up

• Imaging

Cross Cutting Issues

• Communications• Surveillance• Social Determinants and Health Disparities• Genetic Testing• Decision Making• Evidence Based Healthcare• Quality of Cancer Care• Epidemiology

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http://www3.cancer.gov/prevention/

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http://camp.nci.nih.gov/dccps/

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Epidemiology and Genetics Research Program (EGRP)

EGRP manages a comprehensive program of grant-supported, population-based research that brings to bear the expertise of scientists to increase our understanding of cancer etiology and prevention. Scientists from throughout the United States and internationally are supported.

EGRP

Epigenetic Factors

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MRFB and CTEB

Modifiable Risk Factors Branch

Supports research into factors that may be modifiable, such as diet and nutrition, alcohol, physical activity and energy balance, tobacco, infectious diseases, physical and chemical agents, and medical exposures.

Clinical and Translational Epidemiology Branch

Supports research into clinical factors that influence development of cancer among persons with underlying diseases and conditions; the progression, recurrence, and mortality from cancer; and new primary cancers.

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HSFB and MTB

Host Susceptibility Factors Branch

Supports research on personal susceptibility factors such as genetic, epigenetic, immunological and hormonal biological pathways, and social, cultural and race/ethnic factors.

Methods and Technologies Branch

Supports research into methods addressing epidemiologic data collection, study design and analysis, and to modify technological approaches developed in the context of other research endeavors for use as biomarkers and methods to understand cancer susceptibility.

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Special Populations in EGRP

African-American men & women

South American women

Asian-American & Asian men & women

Latin-American/Hispanics

African men & women

Alaskan & Hawaiian Natives

Middle-Eastern populations

American-Indian, incl. Navajo

Rural South

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EGRP Studies Are Everywhere

• Senegal

• Malawi

• The Zambia

• China

• Japan

• Egypt

• Israel

• Brazil

• Colombia

• England

• Canada• Sweden• Denmark• France• Costa Rica• Singapore• Poland• U.S., including Alaska

& Hawaii

2.3 Million SubjectsCohorts, CGN and Family Registries

The Cohort Consortium (CoCo)

• 37 cohorts, over 4 million individuals

• Membership: cohort studies worldwide with >10,000 subjects, blood samples and questionnaire data on important cancer risk factors

• The Cohort Consortium was formed by NCI to address the need for large-scale collaborations for

– Rapid identification and confirmation of common polymorphisms and cancer susceptibility (GWAS)

– Studies of GxG and GxE interactions in the etiology of cancer.

Tw o in te r n a tio n a l C a n c e r Fa m ily R e g is tr ie s (C F R s ) p ro v id e a n in fra -s tru c tu re fo r in te rd is c ip lin a r y re s e a rc h in th e g e n e tic s a n d e p id e m io lo g y o f b re a s t/o va r ia n a n d c o lo n c a n c e r. E a c h o f th e C F R s h a s e p id e m io lo g ic , fa m ily h is to r y, c lin ic a l d a ta , a n d b io s p e c im e n s o n m o re th e 6 ,0 0 0 fa m ilie s , a m o n g w h o m th e re is a h is to r y o f b re a s t a n d /o r o va r ia n c a n c e r o r c o lo n c a n c e r.C F R s s u p p o r t c o lla b o ra tive in ve s tig a t io n s o n :Id e n t if ic a t io n o f n o ve l c a n c e r s u s c e p tib ility g e n e s th ro u g h lin k a g e a n d a s s o c ia tio n s tu d ie sC h a ra c te r iz a t io n o f k n o w n c a n c e r s u s c e p t ib ility g e n e s , in c lu d in g p o p u la t io n fre q u e n c y, p e n e tra n c e , a n d g e n o ty p e -p h e n o ty p e c o rre la tio n sS tu d y o f g e n e -g e n e a n d g e n e -e n v iro n m e n t in te ra c tio n s in b re a s t, o va r ia n , a n d c o lo re c ta l e tio lo g yC o o p e ra tive re s e a rc h o n th e tra n s la t io n a l, p reve n tive , b e h a v io ra l, a n d c o m m u n ic a tio n a s p e c ts o f s u c h fin d in g sH e a lth p o lic y a n d p u b lic h e a lth re s e a rc h .T h e y a ls o p a r tic ip a te in p reve n t io n a n d a s s e s s m e n t s tu d ie s b y id e n tify in g a n d re fe rr in g h ig h -r is k p o p u la t io n s .

BC-CFR Participating Sites

Multi-disciplinary Research in the BC-CFR: a Population Laboratory

http://epi.grants.cancer.gov/CFR/

Currently accrued a cohort of over 20,000 patients and their families across the spectrum of risk for breast and colon cancers and population-based or relative controls

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EGRP: 418 fundedVerma: 57 funded (31 pending)

Epigenetic alterations – changes induced in cells that alter expression of the information on transcriptional, translational, or post-translational levels without change in DNA sequence

EPIGENETICS

SAM SAH

DNMT1DNMT3aDNMT3b

Methylation of DNA

Modifications of histones

RNA-mediated modifications

• RNA-directed DNA methylation• RNA-interference mediated

chromatin remodeling• RNAi, siRNA, miRNA …

A

Me

P

U

- acetylation

- methylation

- phosphorylation

- ubiquitination

P UMe

A

Control Treated-3.0 3.00

Map of the Human Mitochondrial DNAD-loop

OL

OH

Cyt b

ND6

ND5

ND4

ND4L

ND3

COXIII

ATP6ATP8COXII

COXI

ND2

ND1

16SrRNA

12SrRNA

ProstatePancreaticColorectal

Thyroid

PancreaticThyroid

PancreaticProstate

ColorectalColorectalPancreatic

ThyroidPancreatic

Thyroid

BladderColorectalPancreatic

OvarianThyroid

ColorectalPancreatic

Thyroid

PancreaticThyroid

BreastColorectalProstateThyroid

BreastHead and

NeckThyroid

Pancreatic

MeduloblastomaThyroid

Colorectal

BladderPancreatic

Thyroid

All cancers examined to date

mtDNA16.6 kb

BreastOvarian

ColorectalPancreatic

ThyroidProstate

OvarianColorectalPancreatic

Thyroid

D-loop

Cyt b

ND6

ND5

ND4

ND4L

ND3

COXIIIATP6

ATP8COXII

COXI

ND2

ND1

16SrRNA

12SrRNA

mtDNA16.6 kb

F

V

L

IMQ

WANCY

DS K

G

R

SL

H

E

TP

A12308GProstate (OR=2.0)Renal (OR=2.5)

G10398ABreast (OR=1.6)Prostate (OR=19.8)

T4216C

SNP InteractionBreast (OR=3.1)African-Americans

Caucasians

African-Americans

Singh (2007) In: Cancer Epidemiology (Verma, M, ed.). Humana Press.

Epidemiologyand mtDNA

NIHNIH……Turning Discovery Into HealthTurning Discovery Into Health

vermam@mail.nih.gov

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Questions?